Fungicidal nicotinium salt compositions



'cluding yeasts and Actinomycetes),

Patented Feb. 13, 1951 FUNGICIDAL NICOTINIUM'SALT" COMPOSITIONS Leopold-Wen, Philadelphia, andCl arles E. Wood-1 ward, Ahington, Pa., and. Frank; L. Howard, Kingston, and Harry L. Keil wakefield R; L, assignors to Unitedlstates of America as rep resented by, the, Secretary ofAgriculture No Drawing. Original application,December;-

1945, Serial No; 633,027. Divided and this an;- plicationAngust 1 2, 1949, Serial Np, 110,62,-

l i This, application is; made under the: act. of lift-arch}, 1883, as amended by the act of- April 39,; 1928, and the invention herein described, if patented, may-be manufactured and, used by or ioi the Government of the: United States of America; for. governmental purposes without. the payment to us of any. royalty thereon.

This application is adi-vision of our copendins-application, SerialNo. 633,027, filed Decem: bat 9. 5 hich hasm ur d into Patent No.

ihis; nve t on. rel t s to u icid omposi: tions, and more; particularly, to. fungicidal compositions containing nicotinium; salts, and; has among its objects theproyision of such composi- Q l fflr 1 5 1-11 a icul re. and dust y. th r bl P5,-,W a arent rcm the d scr ptionoi the invention.

Nicotine has long been employed for combating insects and is particularlyeffective as a conac nt and/o mi ant a a n an p c s at Small chodied. insectsl S e a fix d nicotine? compositions, such as nicotine .bBIl-e toniteand nicotine ,tannate, have bBQIISIlGCBSS', fully usedin protecting plant surfaces, wherein a.. 1a1sc.ng d pos t o he toxicantis. desir b e, a ain t hew n i s ts.

Thevariousnicotine insecticides usedin the prior art, however,,,haveexhibited littleor no fun ic dal c i it r xampl icotin btntonite is effective in thecontrol of thecodling moth, but it has little or no effect on thefungi whichattack apple trees and fruit. Furthermore, attemptsto incorporate conventional basic fungicides 1 350 applications of fixed nicotine compositions have generally resulted in a disadvanta eous loss of nicotine with a correspondingly decreasedinsecticidal efiectivenessl In addition, in ury to plant foliage is usually increased.

We have found that certain non-metallic derivatives of nicotinewhich are represcntedby the rmula,

Nicotine ,(RX)

wherein R is a monovalent radical selected from the group consisting of alkyl, aralkyl, and substituted aralkyl, and X is a member selected from the group consisting of chloride, bromide, iodide, cyanide, thiocyan-ate, and fatty acid anions, said fatty acid anion having from 2 to -18 carbonatoms, when incorporated in a carrier, areefficient in the control of insects, fungi (inbacteria,

and nematodes. Examples-of such derivatives "are butyl nicctinium bromida'lauryl nieotinium bromide, benzyl nicotinium chloride, o-chloroamended April so, 1928.;.3701,0.,G.{7);

benzyl nicctinium bromide, p-nitrobenzyl nico: tinium bromide; butyl nicotinium thiocyanate; octyl ,nicotinium 1 thiocyanate, lauryl nicotinium, thiocyanate, cetyl nicotiniumthiocyanate, octadecyl znicotinium.,thiocyanate, benzyl nicotinium thiocyanatau o-chlorobenzyl nicotinium thio x cyanate, p-nitrobenzyl nicotinium thiocyanate; benzyl; nicotinium bromide, benzyl, nicotinium almitate enzy nico i um stearata, enzyl nicotinium; oleate, D: nitrobenzyl nicotiniun palmitatc meth nico iniu st ar ia o ia y iw in u tate: c a ec 'ni qi n um' ale" ate, octadecyl nicotinium laurate, lauryl nicotinium propionata: lauryl nicotiniurn oleate, pchlorobenzyl nicotinium chloride, 2;4-dichlorobenzyl nicotinium chloride, 3,4-diehlorobenzyl nicotinium chloride, and 'cetyl 'nicotinium oleate; The carrierwhich is employed is a selective material or materials, into which the nicotine derivative is" incorporated to form the fungicidal composition, and may be an adjuvant, sol vent, coupling agent, dust, oriother materialfo materials chosen for a particular. intended use so a to obtain maximumeil eot ive use ot the wtoxig cant incorporated therein.

The alkyl nicotinium halides were prepared by:

reaction :of equimolecular. quantities of nicotine and the corresponding;alkylhalideg The aralkjyl nicotinium halides and" substituted;v aralkyl nicotinium halides were: prepared; in a;.siIni-lar manner. The preparation of the. nicotinium salts haying thiocyanate or fatty, acid ianions was accomplishedby reaction of the corresponda 11 g ni o i halide in-e u m lec lar 12 7 1 tions with the sodium salt of thiocyanic acid and of the fatty; acid, respectively,

Since there are two- N-heterocyclicnuclei-in I the nicotine molecule, Bxjrnayhe theoretically attached to either thenitrogen of thep'yridine nucleus or thQuHitIOgQn, of th N-methyl 'pyrrolidine nucleus, Since I the latter nitrogen atom is the more basic, it is believed that most of the X, is attache to the ni r gen, Q t e -methyl drop of known volume and I toxicant content,

rather than by spraying on the slides. Macrosporium sarcinaejorme Cav. spores were used as the test fungus, and counts of spores germinated were made and plotted on a logarithmic-probability scale, so that a straight line probability icurve could be obtained, thus making possible the determination of points not found experimentally by interpolation and extrapolation. The concentration of the various nicotinium salts required to kill 50 percent (LD 50) and 90 per cent (LD 90) of the spores (fungitoxicity), were generally obtained by this procedure.

In order to establish the fact that the nicotinium salts were relatively non-injurious to plant organs at concentrations sufiiciently toxic to certain micro-organisms, phytotoxicity, tests were made on succulent uninjured Comet tomato leaves in a greenhouse. The leaves were dipped in a given solution of the toxicant for five seconds, and the percentage of killed tissue observed after five days. The concentrations of nicotimum salts were plotted against percentages of devitalized tissue on a logarithmic-probability scale, and the LD 50 values (phytotoxicity), that is, the concentration of nicotinium salts which killed 50 percent of the leaf tissue area, were obtained by inspection of the resulting graphs.

- The fungitoxicity and phytotoxicity data obtained on some of the nicotinium salts employed are summarized in the following table:

Efiect of the composition and structure of nicotinium derivatives on their ability to inhibit the germination of Macrosporium sarcinaeforme spores and on their injuriousness to tomato foliage Fungitoxicity Phytm Compound toxicity, LD50 LD90 L135 butyl nicotinium bromide. 560 820 2. 2 lauryl nicotinium bromide 9 13 0.27 benzyl nicotinium chloride 210 300 2.05 o-chlorobenzyl nicotinium bromide- 125 190 3.1 g-nitrobenzyl nicotinium bromide 74 105 1. 7 utyl nicotinium thiocyanate 760 1000 4. 8 'octyl nicotinium thiocyanate 31 '52 0.33 lauryl nicotinium thiocyana't 8 0.38 c'etyl nicotinium thiocyanate. 11 32 0. octadecyl nicotinium thiocyanate--- l5 37 0. 43 benzyl nicotinium thiocya'nate 120 160 4. 2 o-chlorobenzyl nicotinium thiocyae n e 130 200 9.0 p-nitrobenzyl nicotinium thiocyanate 85 17.0 'benzyl nicot m 520 690 7. 8 benzyl nicotinium-palmitate- 310 530 2. 9 benzyl'nicotinium stearate.-- 208 230 3. 25 benzyl nicotinium oleate 1500 2000 2. 7 p-nitrobenzyl nicotinium pal tate- 240 370 4. 5 methyl nicotinium stearate. 340 1200 10. 3 octadecyl nicotinium acetate 21 27 0.72 octadccyl nicotinium valerate 25 53 3. l octadec'yl nicotinium laurate 32 50 0.75 lauryl nicotinium propionate. 12 36 0.43 lauryl nicotinium oleate 11 p chlorobenzyl nicotinium chloride- 100 2,4'dichlorobenzyl nicotinium chloride 3,4-dich1orobenzyl nicotinium chloride ' Parts per million required to kill 50 percent of fungus spores. 9 Parts per million required to kill percent of fungus spores. Parts per hundred required to kill a0 percent of tomato leaf area.

The fungitoxicity and phytotoxicity of the nicotinium salts are appreciably affected by the nature of the R and X groups combined with the nicotine. However, in general, all nicotinium salts are effective fungicides, as indicated in the above table. The table indicates, furthermore, that the LD'50 fungitoxicity values are only a very small fraction of the LD 50 phytotox'icity .values, thereby establishing the desirable margin of safety between the toxicant concentration necessary to control the fungus and the toxicant concentration which is seriously injurious to the host.

Variation in the type of R. and X radicals attached to the nitrogen in the pyridine ring and the pyrrolidin ring markedly affects the surface activity, solubility, and compatibility of the compounds in addition to their insecticidal properties. 'This must be considered in the selection of carriers, such as adjuvants, and the determination of the method of application to meet the specifications of use. However, the majority of the nicotinium'salts herein disclosed are sufliciently soluble or dispersible in water, or can be readily made so by utilizing coupling agents (to be described hereafter) for use as sprays or drenches on plant. organs, in disinfecting solutions, and so forth.

As a preliminary step in commercial operation, it has been found advantageous to dissolve the toxicant in a carrier such as a water-soluble organic solvent hereinafter designated a coupling agent. When the solution of toxicant is added to the water in the final spray mixture, the toxicant is more efficiently and uniformly distributed. Examples of such suitable water-soluble solvents, or coupling agents, for the nicotinium salts herein shown are methyl alcohol, acetone, isopropyl alcohol, methyl ethyl ketone, ethyl alcohol, ethylene glycol monoethyl ether, diethylene glycol monoethyl ether, ethylene glycol monomethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, and diethylene glycol monobutyl ether. These may be used singly or in combination with each other. 1

It was found further that those nicotinium salts having a fatty acid anion as the X substituent in the general formula Nicotine (RX) are soluble in carriers such as vegetable and mineral oils. This unusual characteristic permits the use of these compounds in combination with oils to provide both insecticidal and fungicidal action. These oil solutions of the toxicant and a suitable emulsifying agent produce uniform spray emulsions when added to water with efficient stirring. It. is apparent, therefore, that the nicotinium salts of the invention are effective pesticides which can be applied in aqueous solutions or emulsions. Furthermore, they may be applied also as oil solutions or emulsions and as aerosols.

Compositions having concentrations of one part of toxicant in to 10,000 parts of water may be applied to the foliage of apple trees for the control of the apple scab fungus, Venturia inaequalis, and other pests. At similar concentrations, the compositions may be used in the washing of oranges or apples for the inhibition of pathogens, for the drenching of fiats of onion or similar seedlings, for the prevention of damping-off, and for the finishing of textiles to reduce mildew deterioration. They also can be used on surfaces containing fats or waxes where the prevention of mold growth is desirable, such as on cured meats, hides, or waxes for vegetables.

The oil-soluble members of this group, designated above, are soluble in such organic solvents as dichlorodifluoromethane, diethyl .ether, and methyl chloride, which makes them ideally adapted for use in aerosol form. In this method of dispersion, they can be used for the treatment of tobacco seed beds for the control of downy mildew and for the control of fungous and bat):

terial contaminants in storage and warehouse rooms.

In some instances, the application or incorporation of a pesticide in a carrier such as a dust is desired, as for example in the treatment of seeds or for application to foliage. All members of this generic group of nicotinium compounds may be formulated, with dusts such as pyrophyllite, vegetable flour, talc, clay, bentonite, volcanic ash, and so forth, depending upon the requirements of the particular use. Knowledge of the art is necessary to avoid too great fixation of the toxicant by the adjuvant and hence the lowering of its effective toxicity below the point where control is obtained.

The property of surface activity exhibited by some members of the generic group makesthem peculiarly well suited for the inhibition of fungus growth, in certain instances, Where complete coverage by a film of the toxicant solution'is required, or where penetration into a porous matrix is advantageous, these members of the group are unique. On tomentose plant surfaces or on haircovered animal skins, such fungicidal toxicants possess an advantage over those not inherently surface active.

Having thus described our invention, we claim:

1. A fungicidal composition comprising from 100 to 10,000 parts of a carrier in which is incorporated one part of a nicotinium salt having the general formula Nicotine (RX) wherein R is a member selected from the group consisting of alkyl, aralkyl, and substituted aralkyl radicals, and X is a thiocyanate anion.

2. The composition of claim 1 wherein R is an alkyl radical.

3. The composition of claim 1 octyl.

4. The composition of claim 1 lauryl.

5. The composition of claim 1 cetyl.

6. The composition of claim 1 octadecyl.

7. The composition of claim 1 p-nitrobenzyl.

wherein R is wherein R is wherein R is wherein R is LEOPOLD WEIL. CHARLES F. WOODWARD. FRANK L. HOWARD. HARRY L. KEIL.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,048,885 Oakeshott July 28, 1936 2,463,666 Woodward et a1 Mar. 8, 1949 2,466,788 Howard et a1. Apr. 12, 1949 OTHER REFERENCES Hansberry et al.: J. Econ. Ent., vol. 34, No. 1, pages 8083, Feb. 1941.

wherein R is 

1. A FUNGICIDAL, COMPOSITION COMPRISING FROM 100 TO 10,000 PARTS OF A CARRIER IN WHICH IS INCORPORATED ONE PART OF A NICOTINIUM SALT HAVING THE GENERAL FORMULA 